Abstract
A novel myeloid antigen presenting cell can be generated through in vitro haematopoiesis in long‐term splenic stromal cocultures. The in vivo equivalent subset was recently identified as phenotypically and functionally distinct from the spleen subsets of macrophages, conventional (c) dendritic cells (DC), resident monocytes, inflammatory monocytes and eosinophils. This novel subset which is myeloid on the basis of cell surface phenotype, but dendritic‐like on the basis of cell surface marker expression and antigen presenting function, has been tentatively labelled “L‐DC.” Transcriptome analysis has now been employed to determine the lineage relationship of this cell type with known splenic cDC and monocyte subsets. Principal components analysis showed separation of “L‐DC” and monocytes from cDC subsets in the second principal component. Hierarchical clustering then indicated a close lineage relationship between this novel subset, resident monocytes and inflammatory monocytes. Resident monocytes were the most closely aligned, with no genes specifically expressed by the novel subset. This subset, however, showed upregulation of genes reflecting both dendritic and myeloid lineages, with strong upregulation of several genes, particularly CD300e. While resident monocytes were found to be dependent on Toll‐like receptor signalling for development and were reduced in number in Myd88‐/‐ and Trif‐/‐ mutant mice, both the novel subset and inflammatory monocytes were unaffected. Here, we describe a novel myeloid cell type closely aligned with resident monocytes in terms of lineage but distinct in terms of development and functional capacity.
Highlights
Myelopoiesis is a regulated process of cell development leading to multiple cell types which contribute to both innate and adaptive immunity
“L‐dendritic cells (DC)” show upregulation of many genes with functional roles in antigen processing and presentation to Thy1.2 antibody/108 cells (T cells), while resident monocytes show upregulation of genes previously described in relation to monocyte and macrophage function
Spleen resident monocytes are shown to be closely related to a novel APC subset described here as “L‐DC,” such that the two subsets may be derived from a common progenitor or lineage.[104]
Summary
Myelopoiesis is a regulated process of cell development leading to multiple cell types which contribute to both innate and adaptive immunity. Monocytes in blood and spleen are thought to derive from myeloid precursors in bone marrow.[7] Two main subsets of circulating monocytes in blood are present in spleen: the CX3CR1loLy6Chi inflammatory or classical monocytes, and the CX3CR1hiLy6C− resident or non‐classical monocytes.[9] Phenotypic identity of the two main monocyte subsets in spleen was recently clarified in this lab through marker phenotype and functional analysis.[15,16,17] That study classified splenic macrophages as CD11blo cells, with distinct macrophage subsets identifiable through staining with specific subset markers of SIGNR1, MOMA‐1, CD69 and F4/80.17. While it is found to be closely related to resident and inflammatory monocytes, evidence presented here distinguishes it as developmentally and functionally distinct
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